USCAP 2014 Common problems in bone and soft tissue pathology: Cartilage tumors
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1 USCAP 2014 Common problems in bone and soft tissue pathology: Cartilage tumors Andrew Horvai MD PhD Clinical Professor, Pathology UCSF, San Francisco, CA
2 Outline Common intramedullary tumors Enchondroma Conventional chondrosarcoma Chondrosarcoma variants Dedifferentiated chondrosarcoma Mesenchymal chondrosarcoma Clear cell chondrosarcoma (Chondroblastoma to be discussed with giant cell rich lesions) Pitfalls and controversies Grading Malignant transformation from benign tumors Cartilage tumors of small bones of hands and feet
3 Principles: Definitions Unifying characteristics Collagen II Proteoglycan matrix 65% water Aggrecan most common Chondrotoin and Keratan sulfate side chains
4 Principles: Radiology Ring-like calcifications
5 Principles: Treatment Enchondroma Grade 1 chondrosarcoma, chondroblastoma Grade 2-3 chondrosarcoma Observation Curettage and cement Wide local excision +/- chemo Dedifferentiated chondrosarcoma Wide local excision + chemotherapy Mesenchymal chondrosarcoma Wide local excision + chemotherapy Clear cell chondrosarcoma Wide local excision
6 Principles: Syndromes Syndrome MOI* Locus Genes Associated conditions Ollier disease Sporadic 2q33, 15q26 IDH1, IDH2 Maffucci syndrome Sporadic Spindle cell hemangiomas (Glomangiomas Angiosarcomas Hepatobiliary) Malignant transformation 15-20% 20-30% Multiple hereditary exostoses (osteochondromas) Autosomal 8q24, dominant 11p11 EXT1, EXT2 Deformities of forearm, knee, short stature 5-35% *MOI: Mode of inheritance
7 Ollier s / Maffucci s syndrome
8 Malignant transformation of sporadic cartilage tumors Enchondroma: Case reports, <<1% Osteochondroma: 1-8%
9 Case A 16 year old girl, incidentally discovered proximal tibia lesion No pain, no palpable mass.
10 Case A
11 Case A
12 Enchondroma Clinical Radiology Histology Ddx Age: All Loc: Hands/feet, long tubular bones ~3% of adults Metaphysis Lytic, lobular Ring calcifications Intact cortex Lobular Peripheral ossification No permeation Low cellularity No atypia/mitoses Grade 1 Chondrosarcoma
13 Pitfalls: Enchondroma Necrosis Mucin in lacunae
14 Pitfalls: Enchondroma Binucleation enchondroma chondrosarcoma
15 Case B 57 year old man with painful hip for 2 months Needle biopsy performed of acetabular mass
16
17
18 Case B
19 Case B
20 Conventional chondrosarcoma Clinical Radiology Histology Ddx Age: 50+ Loc: pelvis, metadiaphysis long bones Large (> 5 cm) Cortical disruption Endosteal scalloping Soft tissue extension Permeates viable, lamellar bone Myxoid change Hypercellular Atypia open chromatin Mitoses Enchondroma Clear cell chondrosarcoma Chondroblastic osteosarcoma
21 Grade 1 chondrosarcoma or enchondroma? Histology Radiology Molecular Pathology
22 Enchondroma or Grade I chondrosarcoma: Histology Kappa ~ 0.5 Two features >95% sensitivity and specificity Permeation = host bone entrapment > 20% myxoid matrix Eefting D et al. Am J Surg Pathol :50-57
23 Chondrosarcoma: Permeation Enchondroma: Multiple nodules of hyaline cartilage separated by normal marrow (and) plates of lamellar bone that conform to the irregular shapes of cartilage lobules. Chondrosarcoma: Single confluent mass of cartilage trapping host lamellar bone or invasion into Haversian or Volkman systems. - J. Mirra (1985) Pitfalls Small biopsy Curettage Endochondral ossification Mirra JM et al. Clin Ortho Rel Res :
24 Permeation: host bone entrapment
25 Chondrosarcoma: permeation Permeation Enchondral ossification
26 Permeation
27 Chondrosarcoma: Myxoid change
28 Enchondroma or Grade 1 chondrosarcoma: Radiology Most predictive Least predictive Pathologic fracture Axial skeleton Infiltrating margin Soft tissue mass Size > 5 cm Lobulated contour Periosteal reaction Cortical disruption or thickening Deep endosteal scalloping Murphey MD et al. Radiographics (5): Brien EW et al. Skeletal Rad 1997; 26(6) Giuffrida AY et al. J Bone Joint Surg Am :
29 Enchondroma or Grade I chondrosarcoma: Molecular Genetic and molecular features: Karyotype: (C.H.A.M.P. study) Enchondroma (n=14) and CHUMP (n=3): karyotypically normal Grade I chondrosarcoma: Numerical and structural aberrations (n=3). Comparative genomic hybridization: Enchondroma: 13q21; 19, 22q Chondrosarcoma: 2-11, 14, 15, 18, 21 Similar numbers of aberrations Exome sequencing: COL2A1, IDH1, IDH2, TP53 Tallini G et al. J Pathol, 2002; 196(2):194 Ozaki T et al. Anticancer Res 2004; 1721 Amary MF et al. J Pathol. 2011; 334. Szuhai, et al. Cancer Genet 2012; 193. Tarpey PS et al. Nat Genet 2013; 923.
30 Chondrosarcoma: Grading PROGNOSTIC FACTORS IN CHONDROSARCOMA OF BONE A Clinicopathologic Analysis with Emphasis on Histologic Grading HARRY L. EVANS, M.D.* ALBERTO G. AYALA, MD AND MARVIN M. ROMSDAHL, MD, PHD Cancer 40: , Histology 5 year survival 10 year survival Grade 1 Hypercellular, uniform but hyperchromatic nuclei, nuclear detail not visible Grade 2 Diffusely hypercellular, nuclei paler with visible intranuclear detail Grade 3 Sheets of cells, larger nuclei, mitotic activity > 2mf/10 hpf 43 29
31 Grade 1 Chondrosarcoma
32 Grade 2 Chondrosarcoma
33 Grade 3 Chondrosarcoma
34 Pitfall: cartilage tumors of the hands and feet Enchondroma of hands and feet Clinical: Very common site (~30%), painful, pathologic fracture common Radiographs: Cortical erosion common Histology: Hypercellular, myxoid change, nuclear hyperchromasia, permeation within medulla
35 Enchondroma of the phalanx
36 Enchondroma of the phalanx
37 Summary: chondrosarcoma of small bones of hands and feet Metacarpals, metatarsals, wrist and ankle: Soft tissue extension, Grade 3 cytology Behavior similar to chondrosarcoma grade 1 at other sites Phalanges: Soft tissue extension Metastatic rate is very low (<2%) Local resection is favored over amputation whenever possible. Ogose A et al. Cancer, (1):50-9 Ostrowski ML et al. Am J Surg Pathol, (6): Bovee JV et al.cancer, (9):
38 Dedifferentiated chondrosarcoma
39 Dedifferentiated chondrosarcoma
40 Dedifferentiated chondrosarcoma
41 Dedifferentiated chondrosarcoma Clinical Radiology Histology Ddx Age: Adult >50 Loc: Pelvis>Femur> Humerus 5 year survival < 10% Metaphysis Bimorphic (especially on MRI) Abrupt transition: 1. Chondrosarcoma grade 1 2. osteosarcoma/ MFH / fibrosarcoma Chondroblastic osteosarcoma -Less abrupt transition -High grade chondroid component Mesenchymal chondrosarcoma -Young patients -Benign cartilage islands -Less abrupt transition
42 Dedifferentiated chondrosarcoma ~100% mortality Chondroblastic osteosarcoma ~30% mortality
43 Mesenchymal chondrosarcoma
44 Mesenchymal chondrosarcoma
45 Mesenchymal chondrosarcoma
46 Mesenchymal chondrosarcoma Clinical Radiology Histology Ddx Age: Loc: Jaw, rib, pelvis, soft tissue Multifocal 10yr survival 25% Variable course Lytic Ring calcifications Rarely circumscribed 1. Benign cartilage islands/perivascular 2. Small round blue cell tumor HPC-ish vessels common Ewing sarcoma Dediff chondrosarc Small cell osteosarcoma Genetics: Inv(8q21.1;8q13.3) HEY1-NCOA2 Wang L, Genes Chromosomes Cancer 51:127.
47 Clear cell chondrosarcoma
48 Clear cell chondrosarcoma
49 Clear cell chondrosarcoma Clinical Radiology Histology Ddx Age: M>F Loc: Proximal femur Skull, rib, spine Slow growing ~25% Metastasize ~15% mortality Epiphysis Circumscribed Early: lytic, septae Late: sclerotic Permeates Osteogenic No hyaline cartilage Clear cells, well defined membrane, macronucleoli Chondroblastic osteosarcoma Osteoblastoma Chondroblastoma (radiology Ddx)
50 Take-home messages Correlation of radiologic, clinical and histologic features are critical, especially in low-grade cartilage lesions. Permeation is the most sensitive histologic criterion separating enchondroma from chondrosarcoma. Chondrosarcoma of small bones of the hands and feet should be diagnosed with caution. Chondrosarcomas, especially grade 1, are predominantly locally aggressive, but local disease can be fatal even in the absence of metastases
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